Right anterior mini thoracotomy approach for isolated aortic valve replacement: Early outcomes at a Canadian center.

OBJECTIVE: The goal of this manuscript was to report the clinical outcomes of the initial series of 100 consecutive Right Anterior Mini Thoracotomy (RAMT) aortic valve replacement (AVR) implantations at a Canadian Center. METHODS: This retrospective study reported the clinical outcomes of the first 100 patients who underwent the RAMT approach for isolated surgical AVR in Calgary, Canada, between 2016 and 2020. Primary outcomes were death within 30 days of surgery and disabling stroke. Secondary outcomes included surgical times, the need for permanent pacemaker (PPM), incidence of postoperative blood transfusion in the intensive care unit (ICU), postsurgical atrial fibrillation (AF), length of ICU/hospital stay, postsurgical AF, residual paravalvular leak (PVL), postoperative transvalvular gradient, need for postsurgical intravenous opioids, duration of invasive ventilation in the ICU, and chest tube output in the first 12 h postsurgery. RESULTS: In this study, 54 patients were male, and the average age of the cohort was 72 years. Mortality within 30 days of surgery was 1% with no disabling postoperative strokes. Mean cardiopulmonary bypass and cross clamp was 84 and 55 min, respectively. PPM rate was 3%, incidence of blood transfusion in the ICU was 4%, and the rate of postoperative AF was 23%. Median length of ICU and hospital stay was 1 and 5 days, respectively. Rate of mild or greater residual PVL was 3%, while the average residual transvalvular mean gradient was 8.5 mmHg. CONCLUSION: The sternum-sparing RAMT approach can be safely integrated into surgical practice as a minimally invasive alternative for isolated AVR, and can reduce postoperative bleeding and narcotic requirements.

Another Whipple's triad? Pericardial, myocardial and valvular disease in an unusual case presentation from a Canadian perspective.

BACKGROUND: Whipple's disease is a clinically relevant multi-system disorder that is often undiagnosed given its elusive nature. We present an atypical case of Whipple's disease involving pan-valvular endocarditis and constrictive pericarditis, requiring cardiac intervention. A literature review was also performed assessing the prevalence of atypical cases of Whipple's disease. CASE PRESENTATION: A previously healthy 56-year-old male presented with a four-year history of congestive heart failure with weight loss and fatigue. Notably, he had absent gastrointestinal symptoms. He went on to develop pan-valvular endocarditis and constrictive pericarditis requiring urgent cardiac surgery. A clinical diagnosis of Whipple's disease was suspected, prompting duodenal biopsy sampling which was unremarkable, Subsequently, Tropheryma whipplei was identified by 16S rDNA PCR on the cardiac valvular tissue. He underwent prolonged antibiotic therapy with recovery of symptoms. CONCLUSIONS: Our study reports the first known case of Whipple's disease involving pan-valvular endocarditis and constrictive pericarditis. A literature review also highlights this presentation of atypical Whipple's with limited gastrointestinal manifestations. Duodenal involvement was limited and the gold standard of biopsy was not contributory. We also highlight the Canadian epidemiology of the disease from 2012 to 2016 with an approximate 4% prevalence rate amongst submitted samples. Routine investigations for Whipple's disease, including duodenal biopsy, in this case may have missed the diagnosis. A high degree of suspicion was critical for diagnosis of unusual manifestations of Whipple's disease.

Hemodynamic performance of the St. Jude Medical Epic Supra aortic stented valve.

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the hemodynamic performance of the St. Jude Medical Epic Supra bioprosthesis during the early six-month follow up period, and to confirm the safety and efficacy of the valve by collecting details of adverse events and NYHA functional classification. METHODS: Fifty-seven patients undergoing aortic valve replacement (AVR) with the Epic Supra valve between September 2007 and January 2009 at three centers in Canada were evaluated for the study. The subjects were monitored preoperatively, at discharge, and at six months postoperatively. Echocardiographic data were available from 50 subjects at the six-month follow up. In order to prevent observer variability, all echocardiograms were sent to an independent Echocardiography Core Laboratory (ECL) for interpretation of the data. RESULTS: The mean subject age was 74 years. Concomitant coronary artery bypass grafting (CABG) was performed in 44% of the procedures. The mean pressure gradients were 11.2, 12.5, 10.8, 8.4 and 11.3 mmHg, respectively, for valves sized 19 mm (n = 2), 21 mm (n = 20), 23 mm (n = 22), 25 mm (n = 5) and 27 mm (n = 1). The average effective orifice areas (EOAs) were 1.44, 1.57, 1.69, 1.93 and 1.81 cm2 for the .valves sized 19, 21, 23, 25 and 27 mm, respectively. CONCLUSION: The results of the six-month echocardiographic follow up indicated that the Epic Supra valve offered excellent hemodynamic performance in the 21, 23 and 25 mm sizes. However, additional data are still required for the 19 and 27 mm valves to characterize their performance. The mean gradients and EOA-values were comparable to those of other supra-annular stented tissue valves. The EOA index indicated an absence of prosthesis-patient mismatch, with values in all subjects at or near 0.85 cm2/m2. The percentage of subjects without aortic insufficiency (AI) at follow up was 92%; only four subjects showed trivial AI.

Review of Contemporary Techniques for Minimally Invasive Coronary Revascularization.

Minimally invasive coronary revascularization techniques aim to avoid median sternotomy with its associated complications, while facilitating recovery and maintaining the benefits of surgical revascularization. The 3 most common procedures are minimally invasive coronary artery bypass grafting, totally endoscopic coronary artery bypass, and hybrid coronary revascularization. For a variety of reasons, including cost and technical difficulty, not many centers are routinely performing minimally invasive coronary revascularization. Nevertheless, many studies have assessed the safety and efficacy of each of these procedures in different clinical contexts. Thus far results have been promising, and with the evolution of procedural techniques, these approaches have the potential to redefine coronary revascularization in the future. This review highlights the current state of minimally invasive coronary revascularization techniques by exploring their benefits, identifying barriers to their adoption, and discussing future potential paradigms.

The erythropoietin neuroprotective effect: assessment in CABG surgery (TENPEAKS): a randomized, double-blind, placebo controlled, proof-of-concept clinical trial.

BACKGROUND AND PURPOSE: Neurocognitive dysfunction complicates coronary artery bypass surgery. Erythropoietin may be neuroprotective. We sought to determine whether human recombinant erythropoietin would reduce the incidence of neurocognitive dysfunction after surgery. METHODS: We randomly assigned 32 elective first-time coronary artery bypass graft patients to receive placebo or 375 U/kg, 750 U/kg, or 1500 U/kg of recombinant human erythropoietin divided in 3 daily doses, starting the day before surgery. Primary outcomes were feasibility and safety, and secondary outcomes were neurocognitive dysfunction at discharge and 2 months. RESULTS: All subjects were male, mean age 60 years (range 46 to 73). No significant differences were found in pump time, cross-clamp time, or hospital length of stay. Mortality and pure red cell aplasia were not observed. One patient in the 375 U/kg group had ST changes compatible with myocardial injury immediately postoperative, but no other thrombotic complications were observed. Neurocognitive dysfunction occurred in 21/32 (66%) of patients at discharge and 5/32 (16%) at 2 months. Neurocognitive dysfunction at discharge by group was: placebo 6/8 (75%), 375 U/kg 4/8 (50%), 750 U/kg 6/8 (75%), and 1500 U/kg 5/8 (63%). Neurocognitive dysfunction at 2 months by group was: placebo 3/8 (38%), 375 U/kg 1/8 (13%), 750 U/kg 1/8 (13%), and 1500 U/kg 0/8 (0%). Neurocognitive dysfunction at 2 months for erythropoietin at any dose was 2/24 (8.3%) versus 3/8 (38%) for placebo (P=0.085). CONCLUSIONS: This study demonstrates feasibility and safety for the use of human recombinant erythropoietin as a neuroprotectant in coronary artery bypass graft surgery. A trend in the reduction of neurocognitive dysfunction at 2 months was associated with erythropoietin use. A multicenter randomized controlled trial is warranted.

Perceval Valve Implantation: Technical Details and Echocardiographic Assessment.

The Perceval valve (LivaNova, London, United Kingdom) is a collapsible, sutureless bioprosthetic aortic valve. This novel design is well suited for minimally invasive approaches and has particular advantages for patients with small, calcified annuli. The implantation technique is unique, and echocardiographic assessments of valve cage shape, angulation, and height are essential. The following discussion provides a framework of technical and sonographic considerations to help surgical teams achieve reproducible success with Perceval valve deployment.

Automated Referral to Cardiac Rehabilitation After Coronary Artery Bypass Grafting Is Associated With Modest Improvement in Program Completion.

BACKGROUND: Cardiac rehabilitation (CR) is a guideline-indicated modality for reducing residual cardiovascular risk among patients undergoing coronary artery bypass grafting (CABG) surgery. However, many referred patients do not initiate or complete a CR program; even more patients are never even referred. METHODS: All post-CABG patients in Calgary, Alberta, Canada, from January 1, 1996, to March 31, 2016, were included. Data were obtained from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease and TotalCardiology Rehabilitation databases. Automated referral to CR at discharge after CABG was instituted on July 1, 2007. We used interrupted time series analysis to evaluate the impact of automated referral on CR referral and completion rates and studied the association of these CR process markers with mortality. RESULTS: A total of 8,118 patients underwent CABG surgery during the study period: 5,103 before automation and 3,015 after automation. Automation increased referral rates from 39.5% to 75.0% (P < 0.001). Automated referral was associated with a 7.2% increase in CR completion in the overall population (33.3% vs 26.1%; P < 0.001). In adjusted models, CR referral alone was not associated with reduced mortality (hazard ratio [HR] 0.84, 95% CI 0.64-1.11), but CR completion was (HR 0.43, 95% CI 0.31-0.61). CONCLUSION: Automated referral in post-CABG patients resulted in modest improvement in CR program completion. Therefore, even when CR referral is automated to include all eligible patients, additional strategies to support CR program enrollment and completion remain necessary to achieve the desired health benefits.

Duodenal ulcers are a major cause of gastrointestinal bleeding after cardiac surgery.

OBJECTIVE: To determine the incidence of gastrointestinal (GI) bleeding in patients after cardiac surgery, assess the perioperative risk factors, and determine the type of GI tract pathology associated with bleeding events. METHODS: At a tertiary referral hospital, all cardiac surgery patients having a postoperative GI bleed from April 2002 to March 2012 were identified. To determine bleeding etiology, only patients requiring endoscopy were included in the analysis. By retrospective review of 3 prospectively maintained databases, the incidence and independent predictors of GI bleeding, as well as endoscopic findings, were determined. RESULTS: Ninety-one GI bleeding events that required endoscopy were identified in 9017 patients. Those that bled were aged 71 ± 12 years, and 76% were men. Sixty-three percent of these patients had valve surgery and 37% had an isolated coronary artery bypass grafting. The overall incidence of GI bleeding was 1.01%, with an upper GI source accounting for 78%. Endoscopy data found a duodenal ulcer as the bleeding source in 71%, whereas stress gastritis accounted for 8%. Preoperative risk factors for bleeding included age ≥70 years, ejection fraction <35%, congestive heart failure, cerebrovascular disease, chronic kidney disease, and gastrointestinal disease. A preoperative history of atrial fibrillation and anticoagulation with Coumadin also was associated with bleeding. Patients that bled had a 30-day mortality rate of 8.8%, which was significantly greater than patients who did not bleed (4.3%; P = .03). CONCLUSIONS: Clinical variables can be used to identify patients at high risk for GI bleeding after cardiac surgery. When GI bleeding occurs, the most common cause is duodenal ulceration, which has an association with Helicobacter pylori infection. These findings may provide an opportunity to initiate preoperative preventative strategies.

A randomized controlled trial of women's early use of a novel undergarment following sternotomy: the Women's Recovery from Sternotomy Trial (WREST).

BACKGROUND: Despite a lack of randomized trial evidence, clinicians often suggest that women use a brassiere to reduce poststernotomy pain and discomfort. We tested the effect of women's use of a special (compression) undergarment after sternotomy on pain, discomfort, and functional status. METHODS: Women (n = 481) having first-time sternotomy in 1 of 10 Canadian centers were randomized to receive the intervention or usual care. Pain and discomfort data (using numeric rating scales) were collected in person while participants were hospitalized. Thereafter, pain, discomfort, and functional status data (using Health Assessment Questionnaire) were collected by standardized telephone interview until 12 postoperative weeks. RESULTS: Overall, and until at least 6 weeks postoperatively, fewer women in the intervention than usual care group reported having incision and breast pain and discomfort. Breast pain scores were lower in the intervention than the usual care group at 2 weeks postoperatively (P = .04), and over time (OR 0.65 [95% CI 0.45-0.94], P = .02). For women discharged within 14 postoperative days, post hoc analyses revealed intervention group patients had a significantly reduced likelihood of breast pain (OR 0.46 [95% CI 0.32-0.66], P < .001) and breast discomfort (OR 0.62 [95% CI 0.44-0.86], P = .01) but not incision pain (OR 0.99 [95% CI 0.72-1.37], P = .95) or discomfort (OR 0.77 [95% CI 0.55-1.02], P = .06). There was no difference between groups in functional status. The effects were not influenced by age or brassiere size. CONCLUSIONS: Using a supportive undergarment during the early postoperative reduces breast pain. This finding is amplified and extends to include a reduction in breast discomfort, when women are discharged within 14 postoperative days.

The Women's Recovery from Sternotomy (WREST) study: design of a randomized trial of a novel undergarment for early use after sternotomy.

BACKGROUND: Clinicians who work with women poststernotomy often suggest that they wear a supportive brassiere to ameliorate pain, discomfort, and potential wound complications. There is no empirical evidence that supports this practice. METHODS: Despite methodological challenges, a clinical trial is currently underway to investigate the efficacy of early use of a novel undergarment after sternotomy. Women (N = 430) having first time sternotomy in 9 Canadian centers will be randomized to receive either the usual care of the institution or early use of a novel undergarment. Follow-up is planned over 12 postoperative weeks. Coprimary outcomes are pain, discomfort, and return to function. Wound healing is a secondary outcome. An economic evaluation substudy is also underway. CONCLUSIONS: The WREST Study is a unique ongoing trial examining the efficacy of a novel undergarment in reducing women's pain and enhancing their comfort and return to function. The findings of the trial and its economic substudy will enable health care providers to make rational evidence-based clinical decisions regarding women's early care after sternotomy.

The association between prior percutaneous coronary intervention and short-term outcomes after coronary artery bypass grafting.

BACKGROUND: Increasingly, patients are being referred for coronary artery bypass grafting (CABG) for management of symptoms after prior percutaneous coronary intervention (PCI). In this study, we assessed the impact of prior PCI on inhospital mortality after CABG. METHODS: Perioperative data were collected on patients who underwent first-time CABG at 2 surgical centers. Patients who underwent PCI and CABG during the same admission were excluded. Patients with prior PCI were compared with patients with no prior PCI, and the risk-adjusted impact of prior PCI on inhospital mortality after CABG was determined using both multivariate techniques and propensity score matching techniques. RESULTS: Six thousand thirty-two patients met inclusion criteria. Patients with prior PCI were less likely to be between the ages of 70 and 80 (P < .0001), to have an ejection fraction <0.40 (P < .0001), and to have 3-vessel/left main disease (P < .0001). They were, however, more likely to have Canadian Cardiovascular Society class IV symptoms (P < .0001) and to have an urgent status (P = .02). Rates of inhospital mortality after CABG were higher in patients with prior PCI (3.6% vs 2.3%, P = .02). Using multivariate techniques, prior PCI emerged as an independent predictor of postoperative inhospital mortality (odds ratio 1.93, P = .003). When patients with prior PCI were matched to patients with no prior PCI using propensity scores, inhospital mortality remained higher among patients with prior PCI (3.6% vs 1.7%, P = .01). CONCLUSION: Patients with prior PCI presented for CABG with less comorbidity and diminished coronary disease; yet, they had more advanced symptoms and greater urgency. After adjusting for these differences, prior PCI emerged as an independent predictor of inhospital mortality after CABG.

The preoperative intraaortic balloon pump in coronary bypass surgery: a lack of evidence of effectiveness.

BACKGROUND: There is limited evidence demonstrating the effectiveness of preoperative intraaortic balloon pump (IABP) use in isolated coronary artery bypass graft (CABG) surgery. A single-center randomized trial demonstrated its benefit. We undertook a multicenter observational study to verify this finding. METHODS: In 29,950 consecutive patients undergoing isolated CABG between 1995 and 2000 at 10 centers, we compared patients with and without a preoperative IABP. We also compared the effect of preoperative IABP use within 7 high-risk clinical subgroups. To validate the previous randomized trial, patients with any 2 of the following were also analyzed: left main > 70%, ejection fraction < 40%, redo CABG, or preoperative intravenous nitroglycerin. RESULTS: Preoperative IABPs were used in 1896 patients (6.3%). These patients had more comorbid conditions and a higher crude mortality than those who did not have preoperative IABPs (9.5% vs 2.3%, P < .0001). Preoperative IABP patients were caliper matched to non-preoperative IABP patients using a propensity score. Excess mortality associated with preoperative IABP persisted (9.2% vs 5.8%, P = .0004). In 7 high-risk subgroups, mortality was significantly higher with preoperative IABP. We used propensity caliper matching to compare preoperative IABP with non-preoperative IABP patients who met trial criteria (n = 4332). Preoperative IABP was associated with higher mortality (11.0% vs 6.5%, P = .0009). Removing emergency patients did not alter results. CONCLUSIONS: Use of preoperative IABPs was consistently associated with higher mortality. Despite detailed statistical analysis, we were unable to show benefit from preoperative IABP use or confirm the results of a single-center trial that demonstrated its benefit. Assessment of preoperative IABP efficacy will require a randomized trial.

Outcomes in octogenarians undergoing coronary artery bypass grafting.

BACKGROUND: Although octogenarians are being referred for coronary artery bypass grafting (CABG) with increasing frequency, contemporary outcomes have not been well described. We examined data from 4 Canadian centres to determine outcomes of CABG in this age group. METHODS: Data for the years 1996 to 2001 were examined in a comparison of octogenarians with patients less than 80 years of age. Logistic regression analysis was used to adjust for preoperative factors and to generate adjusted rates of mortality and postoperative stroke. RESULTS: A total of 15,070 consecutive patients underwent isolated CABG during the study period. Overall, 725 (4.8%) were 80 years of age or older, the proportion increasing from 3.8% in 1996 to 6.2% in 2001 (p for linear trend = 0.03). The crude rate of death was higher among the octogenarians (9.2% v. 3.8%; p < 0.001), as was the rate of stroke (4.7% v. 1.6%, p < 0.001). The octogenarians had a significantly greater burden of comorbid conditions and more urgent presentation at surgery. After adjustment, the octogenarians remained at greater risk for in-hospital death (odds ratio [OR] 2.64, 95% confidence interval [CI] 1.95-3.57) and stroke (OR 3.25, 95% CI 2.15-4.93). Mortality declined over time for both age groups (p for linear trend < 0.001 for both groups), but the incidence of postoperative stroke did not change (p for linear trend = 0.61 [age < 80 years] and 0.08 [age > or = 80 years]). Octogenarians who underwent elective surgery had crude and adjusted rates of death (OR 1.31, 95% CI 0.60-2.90) and stroke (OR 1.59, 95% CI 0.57-4.44) that were higher than but not significantly different from those for non-octogenarians who underwent elective surgery. INTERPRETATION: In this study, rates of death and stroke were higher among octogenarians, although the adjusted differences in mortality over time were decreasing. The rate of adverse outcomes in association with elective surgery was similar for older and younger patients.

Is mitral valve surgery safe in octogenarians?

OBJECTIVE: To evaluate the outcomes of mitral valve surgery in octogenarians. METHODS: Data were collected prospectively from January 1996 to March 2004 at two surgical centers. Of 1386 consecutive patients with mitral valve surgery, 58 (4.2%) were aged > or = 80 years. Survival data were analyzed using Cox proportional hazards modeling and Kaplan-Meier actuarial log rank statistics. RESULTS: Octogenarians were similar to younger patients for the presence of pre-operative hypertension, hyperlipidemia, diabetes mellitus, and smoking history. Octogenarians had a higher incidence of cerebrovascular disease (19.0 versus 7.8%, P = 0.003), urgent in-hospital surgery (55.2 versus 28.6%, P < 0.001), and presence of ischemic disease requiring combined mitral valve plus revascularization surgery (72.4 versus 41.0%, P < 0.001). Mitral valve repair was performed in a similar proportion of octogenarians and younger patients (44.8 versus 45.6%). Thirty-day mortality for octogenarians was significantly higher than younger patients (15.5 versus 5.6%, P = 0.002), and actuarial survival of octogenarians was significantly decreased (P = 0.009). However, 52.3% of the octogenarians were alive at 7-years following surgery. Independent predictors of mortality from multivariate risk adjusted modeling of the entire cohort were: emergency surgery (hazards ratio [HR] = 2.94, P < 0.001), combined mitral valve plus revascularization surgery (HR = 2.27, P < 0.001), mitral valve replacement (HR = 1.85, P < 0.01), and age > or = 80 years (HR = 1.80, P = 0.02). CONCLUSIONS: Octogenarians undergoing mitral valve surgery have significantly greater incidence of urgent surgery, ischemic disease requiring combined revascularization surgery, and have decreased rates of survival. While caution is required when operating on these higher risk elderly patients, overall 52.3% of the octogenarians are alive at 7-years following surgery, which is greater than the survival of octogenarians in the community. The greatest survival benefit within octogenarians occurred when mitral valve repair was possible over replacement. Further study will more clearly define subgroups of octogenarians with potentially greater benefit from mitral valve surgery.

Prophylactic Oral Amiodarone for the Prevention of Arrhythmias that Begin Early After Revascularization, Valve Replacement, or Repair: PAPABEAR: a randomized controlled trial.

CONTEXT: Atrial tachyarrhythmias after cardiac surgery are associated with adverse outcomes and increased costs. Previous trials of amiodarone prophylaxis, while promising, were relatively small and yielded conflicting results. OBJECTIVE: To determine whether a brief perioperative course of oral amiodarone is an effective and safe prophylaxis for atrial tachyarrhythmias after cardiac surgery overall and in important subgroups. DESIGN, SETTING, AND PATIENTS: Double-blind randomized controlled trial of 601 patients listed for nonemergent coronary artery bypass graft (CABG) surgery and/or valve replacement/repair surgery between February 1, 1999, and September 26, 2003, at a tertiary care hospital. The patients were followed up for 1 year. INTERVENTION: Oral amiodarone (10 mg/kg daily) or placebo administered 6 days prior to surgery through 6 days after surgery (13 days). Randomization was stratified for subgroups defined by age, type of surgery, and use of preoperative beta-blockers. MAIN OUTCOME MEASURE: Incidence of atrial tachyarrhythmias lasting 5 minutes or longer that prompted therapy by the sixth postoperative day. RESULTS: Atrial tachyarrhythmias occurred in fewer amiodarone patients (48/299; 16.1%) than in placebo patients (89/302; 29.5%) overall (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.34-0.69; P<.001); in patients younger than 65 years (19 [11.2%] vs 36 [21.1%]; HR, 0.51 [95% CI, 0.28-0.94]; P = .02); in patients aged 65 years or older (28 [21.7%] vs 54 [41.2%]; HR, 0.45 [95% CI, 0.27-0.75]; P<.001); in patients who had CABG surgery only (22 [11.3%] vs 46 [23.6%]; HR, 0.45 [95% CI, 0.26-0.79]; P = .002); in patients who had valve replacement/repair surgery with or without CABG surgery (25 [23.8%] vs 44 [44.1%]; HR, 0.51 [95% CI, 0.31-0.84; P = .008); in patients who received preoperative beta-blocker therapy (27 [15.3%] vs 42 [25.0%]; HR, 0.58 [95% CI, 0.34-0.99]; P = .03); and in patients who did not receive preoperative beta-blocker therapy (20 [16.3%] vs 48 [35.8%]; HR, 0.40 [95% CI, 0.22-0.71]; P<.001), respectively. Postoperative sustained ventricular tachyarrhythmias occurred less frequently in amiodarone patients (1/299; 0.3%) than in placebo patients (8/302; 2.6%) (P = .04). Dosage reductions of blinded therapy were more common in amiodarone patients (34/299; 11.4%) than in placebo patients (16/302; 5.3%) (P = .008). There were no differences in serious postoperative complications, in-hospital mortality, or readmission to the hospital within 6 months of discharge or in 1-year mortality. CONCLUSION: Oral amiodarone prophylaxis of atrial tachyarrhythmias after cardiac surgery is effective and may be safe overall and in important patient subgroups. Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00251706.

Impact of preoperative intravenous nitroglycerin on in-hospital outcomes after coronary artery bypass grafting for unstable angina.

BACKGROUND: Intravenous nitroglycerin (NTG) is an effective therapy for unstable angina (UA), but it may induce endothelial dysfunction and impair vascular nitric oxide signaling. We sought to determine whether preoperative intravenous NTG administration alters in-hospital outcomes in patients undergoing coronary artery bypass grafting (CABG) for UA. METHODS AND RESULTS: All in-hospital patients with Canadian Cardiovascular Society class IV angina who had isolated CABG between March 1995 and July 2002 at two Canadian centers were identified (n = 3976). Of these, 2506 were not receiving intravenous NTG and 1470 were receiving intravenous NTG at the time of CABG. Outcomes assessed were in-hospital mortality (IHM), intraoperative or postoperative aortic balloon pump use, perioperative myocardial infarction, prolonged (> or =24 hours) ventilation (p-vent), and a composite outcome, defined as any one or more of the above. Unadjusted IHM (5.9% vs 4.2%, P =.02), p-vent (22.2% vs 10.5%, P =.0001), and composite outcome (26.5% vs 15.2%, P =.0001) were higher in patients receiving intravenous NTG. Logistic regression showed that preoperative intravenous NTG was not an independent predictor of composite outcome (OR, 1.1; P =.49) or IHM (OR, 0.94; P =.69). Propensity score analysis was used to match two subgroups of patients (group 1, intravenous NTG, n = 1176; group 2, no intravenous NTG, n = 1176) on multiple factors. After adjustment with the propensity score, preoperative intravenous NTG use had no significant effect on any of the outcomes assessed. CONCLUSIONS: Despite its potential to induce endothelial dysfunction and impair vascular nitric oxide signaling, preoperative intravenous NTG administration is not associated with altered in-hospital outcomes after CABG for UA.

Increased endothelin-1 production in diabetic patients after cardioplegic arrest and reperfusion impairs coronary vascular reactivity: reversal by means of endothelin antagonism.

OBJECTIVES: Evidence has accrued to suggest that diabetic patients face an increased risk of ischemic events and low output syndrome and might mount an inordinate response to ischemia and reperfusion. Because hyperglycemia is a potent stimulus for endothelin-1 production, we hypothesized that increased production, action, or both of endothelin-1 in diabetes might represent an important mediator of endothelial dysfunction in patients with that disease. To this aim, we compared the effects of cardioplegic arrest and reperfusion on coronary sinus effluent endothelin-1 levels and atrial arteriolar vascular responses in diabetic and case-matched nondiabetic patients undergoing coronary artery bypass grafting. METHODS: In study 1 coronary sinus effluent endothelin-1 levels were assessed at baseline and at 1 and 10 minutes after reperfusion in 13 diabetic and 12 nondiabetic patients matched for age, ejection fraction, Parsonnet score, and crossclamp time. In study 2 vascular responses of atrial arterioles subjected to perioperative ischemia-reperfusion were evaluated with videomicroscopy. Atrial microvessels (from appendages) were obtained before and after removal of the aortic crossclamp, and vascular responses to exogenously administered endothelin-1 (10(-10) mol/L) and substance P (10(-8) mol/L) were studied in the presence or absence of BQ-123, an endothelin A receptor antagonist. RESULTS: Diabetic patients elaborated more endothelin-1 at 1 and 10 minutes after reperfusion (P =.01). Endothelin-1-mediated vasoconstriction was similar in diabetic and nondiabetic atrial microvessels before cardioplegic arrest and cardiopulmonary bypass. After cardiopulmonary bypass and reperfusion, endothelin-1-mediated vasoconstriction was enhanced in both groups; however, this response was greater in microvessels from diabetic patients (P =.02). BQ-123, the endothelin A antagonist, attenuated the effects of bypass and reperfusion on endothelin-1-mediated vasoconstriction in both groups (P =.01). Substance P-mediated vasodilatation was similar in diabetic and nondiabetic atrial microvessels before bypass. After bypass and reperfusion, substance P-mediated vasodilatation was diminished in both groups; however, this response was more pronounced in the diabetic group (P =.003). BQ-123 coincubation restored substance P-mediated vasodilatation in both groups. CONCLUSIONS: We determined the following: (1) the coronary effluent release of endothelin-1 is higher in diabetic than in nondiabetic patients after cardiopulmonary bypass and reperfusion; (2) diabetic coronary microvessels respond to bypass and reperfusion with greater endothelin-1-mediated vasoconstriction and diminished nitric oxide-mediated vasodilatation; and (3) these effects are attenuated by endothelin antagonism. Endothelin-1 might be an important mediator of ischemia-reperfusion injury in patients with diabetes. Furthermore, use of endothelin receptor antagonists might be a novel strategy for improving the resistance of the diabetic heart to cardioplegic arrest and reperfusion.

Novel cardioprotective effects of tetrahydrobiopterin after anoxia and reoxygenation: Identifying cellular targets for pharmacologic manipulation.

OBJECTIVES: Contemporary cardioprotective strategies to prevent perioperative ischemia-reperfusion injury have focused on the l-arginine nitric oxide pathway. Tetrahydrobiopterin is an absolute cofactor required for the enzyme nitric oxide synthase and is thus a critical determinant of nitric oxide production. We hypothesized that ischemia-reperfusion results in diminished levels of tetrahydrobiopterin, which might represent a key cellular defect underlying endothelial and myocyte dysfunction after ischemia-reperfusion. To this aim, we examined the effects of tetrahydrobiopterin supplementation in (1) an in vivo experimental model of global ischemia-reperfusion and (2) an in vitro human ventricular heart cell model of simulated ischemia-reperfusion. Measures of endothelial function, oxidant production, cell survival, and cardiac function were used to assess outcome. METHODS: In study 1 Wistar rats were divided into one of 2 groups (n = 10 per group). One group received tetrahydrobiopterin (25 mg x kg(-1) x d(-1) for 7 days), and the other group served as the control group. Hearts were subjected to 30 minutes of ischemia followed by 30 minutes of reperfusion, and left ventricular developed pressure, left ventricular systolic pressure, and left ventricular end-diastolic pressure were determined by using the modified Langendorff technique. In study 2 we quantitated myocardial malondialdehyde, a marker of lipid peroxidation, in ventricular tissues from both groups of animals using butanol phase extraction and spectrophotometric analysis. In study 3 coronary vascular responses were determined in vascular segments of the left coronary artery in both groups of animals after ischemia-reperfusion. Endothelium-dependent and endothelium-independent vasodilatation to acetylcholine and sodium nitroprusside, respectively, were compared between groups. In study 4, using a human ventricular heart cell model of simulated ischemia-reperfusion, we studied the effects of tetrahydrobiopterin (20 micromol/L) on cellular injury (as assessed by means of trypan blue uptake). RESULTS: After ischemia-reperfusion, myocardial dysfunction was evidenced by a decrease in left ventricular developed pressure and an increase in left ventricular end-diastolic pressure (P =.01 compared with baseline). Hearts from tetrahydrobiopterin-treated rats exhibited protection against ischemia-reperfusion injury (left ventricular developed pressure: 74 +/- 4 vs control 42 +/- 8 mm Hg, P =.01; left ventricular end-diastolic pressure: 12 +/- 3 vs 34 +/- 7 mm Hg, P =.01). Furthermore, tetrahydrobiopterin treatment attenuated the rise in malondialdehyde levels after ischemia-reperfusion (P =.01). After reperfusion, coronary endothelial function to acetylcholine was attenuated (P =.003 vs sham-treated mice), whereas responses to sodium nitroprusside remained unchanged. Tetrahydrobiopterin-treated rats exhibited an improvement in acetylcholine-mediated vasorelaxation (P =.01 vs ischemia-reperfusion group). Cellular injury, as assessed by means of trypan blue uptake, was higher in human ventricular heart cells subjected to simulated ischemia-reperfusion; this effect was prevented with tetrahydrobiopterin treatment (P =.001). CONCLUSIONS: Supplemental tetrahydrobiopterin provides a novel cardioprotective effect on left ventricular function, endothelial-vascular reactivity, oxidative damage, and cardiomyocyte injury after ischemia-reperfusion injury and might represent an important cellular target for future operative myocardial protection strategies.